The removal efficiency of catalytic ozonation of bezafibrate (BZF) by red mud loaded Co catalysts (Co/RM) was used as the index value in statistical experimental designs. The most important factors influencing BZF degradation (P < 0.05) in water were dipping mass of cobalt and calcination temperature. Under the conditions of 4.14% of dipping mass of cobalt and 389 degrees C of calcination temperature, the BZF removal efficiency was 71.29% as calculated by predictive value and a maximum removal efficiency of 70.74% was actually achieved. The experiment data was very close to the predictive value and the deviation was 1% (< 5%). The results indicated that the response surface methodology and mathematical model was reliable for experimental design. By comparing the differences of BZF degradation in RM and Co/RM processes, it was observed that Co/RM exhibited the greater catalytic activity. Furthermore, the surface structure and composition properties of the two catalysts were evaluated by N2 adsorption, XRD and UV-Vis analysis. It was found that the specific surface area and total pore volume had the same variation trend, RM < Co/RM, which was consistent with the trend of catalytic ozonation. It was also found that Co3O4, the active component formed on the surface of RM by the addition of cobalt into red mud, enhanced the catalytic activity. Moreover, the dissolved metal concentration in the solution for catalytic ozonation of BZF degradation by RM or Co/RM was determined by ICP-OES. The results showed that for both catalysts there was no leaching of catalytic active components into the solution, which could suggest that the two catalysts were safe and could have certain application prospect.